Determining the effects of "bath salts" on cognitive control and functional brain connectivity

摘要 “浴盐”或合成卡西酮药物长期使用的潜力，改变行为的能力，如认知 大脑的控制和改变使它们成为一个重要的医疗保健问题。最有害的沐浴之一 盐是3，4-亚甲基二氧基吡咯戊酮（MDPV）。MDPV的不良行为影响可持续数天， 可能是由于多巴胺神经传递的改变。药物研究表明，MDPV是 与可卡因相似，但更持久。然而，MDPV的一个重要的未开发方面是 它如何改变认知控制，以及改变的认知控制是否是一些最严重的 MDPV使用的行为结果。认知控制指的是一组心理过程， 目标导向行为的组织和中介。在这项研究中，两个特定的认知控制领域， 兴趣是灵活性和冲动性。这两个子过程在物质使用障碍中受到损害 并可能导致不受控制的寻药行为。最近，我们使用功能性磁共振成像技术发现，在24小时后， 大鼠急性MDPV给药引起大脑连接性增加，特别是在额叶皮质 诸如眶额（OrF）、边缘下（IL）、边缘前（PL）和皮质下奖赏区的区域，包括 纹状体、杏仁核和杏仁核（NAc）。这些连通性的变化可能是一些 MDPV最危险的影响是通过诱导认知控制大脑连接的长期变化 电路因此，我们假设持续自我给予MDPV将增加功能性 额叶皮质（PL、IL和OrF）、丘脑、杏仁核和NAc之间的连接导致损伤 认知控制功能。我们将使用经过长期自我管理训练的啮齿动物来验证这一假设。 MDPV 10天。拟议的研究旨在解决我们对如何理解的现有差距 MDPV破坏了认知控制以及哪些大脑区域受到最大影响和计算连接 功能磁共振成像的变化。在这个项目中，候选人将评估认知控制的两个子过程， 冲动和灵活性。行为将被分析有关的功能连接的变化， 纵向静息状态fMRI（rsfMRI）数据，以及使用活动的神经元表现依赖性活动 调节大鼠细胞凋亡相关基因（Arc）mRNA的表达。开展拟议的研究将 允许候选人从事独立的研究生涯，整合rsfMRI的纵向研究 连接，行为和Arc细胞分析到药物使用障碍的研究。

Abstract “Bath salts” or synthetic cathinones drugs potential of chronic use, ability to alter behaviors like cognitive control and alterations in the brain makes them a significant healthcare concern. One of the most harmful bath salts is 3,4-methylenedioxypyrovalerone (MDPV). The adverse behavioral effects of MDPV can last days-to- weeks possibly due to alteration in dopamine neurotransmissions. Research into drug has shown that MDPV is similar pharmacologically to cocaine but longer lasting. However, an essential unexplored aspect of MDPV is how it alters cognitive control and whether changed cognitive control underlies some of the most severe behavioral outcomes of MDPV use. Cognitive control refers to a set of mental processes driving the organization and mediation of goal-oriented behavior. In this grant, two specific cognitive control domains of interest are flexibility and impulsivity. These two subprocesses are compromised in substance use disorders and can lead to uncontrolled drug-seeking behavior. Using fMRI, we recently showed that after 24 hours an acute MDPV administration in rats caused an increase in brain connectivity specifically in frontal cortical regions such as orbitofrontal (OrF), infralimbic (IL), prelimbic (PL) and subcortical reward regions including striatum, amygdala, and nucleus accumbens (NAc). These changes in connectivity could underlie some of the most dangerous effects of MDPV by inducing long-lasting changes in the connectivity of cognitive control brain circuitry. Therefore, we hypothesize that sustained self-administration of MDPV will increase functional connectivity between the frontal cortex (PL, IL, and OrF), thalamus, amygdala, and NAc leading to impairments in cognitive control functions. We will test this hypothesis using rodents trained to chronically self-administer MDPV for ten days. The proposed research is designed to address existing gaps in our understanding of how MDPV undermines cognitive control and which brain regions are most affected and calculating connectivity changes in the brain with fMRI. In this project, the candidate will assess two subprocesses of cognitive control, impulsivity, and flexibility. The behavior will be analyzed concerning functional connectivity changes of longitudinal resting state fMRI (rsfMRI) data, and neuronal performance-dependent activity using activity regulated cytoskeletal-associated gene (Arc) mRNA expression in rats. Carrying out the proposed research will permit the candidate to incur in an independent research career integrating longitudinal studies of rsfMRI connectivity, behavioral, and Arc cellular analysis into studies of drug use disorders.